ONC201 + Paclitaxel for Ovarian Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Ira Winer
Must not be taking: CYP3A4 inhibitors/inducers
Disqualifiers: Other active cancers, Serious infection, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This phase II trial studies the side effects of ONC201 and paclitaxel and how well they work in treating patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer that has come back (recurrent), or that does not respond to treatment (refractory). ONC201 is the first in its class of drugs that antagonize some specific cell receptors on cancer cells, leading to their destruction. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ONC201 and paclitaxel may work better in treating patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer compared to paclitaxel alone.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications, but it does mention that you cannot take other chemotherapy, immunotherapy, or hormonal anti-cancer therapies while on the study medications. Additionally, you must stop taking any drugs that are moderate to strong inhibitors or inducers of CYP3A4 at least one week before starting the trial.
What data supports the effectiveness of the drug ONC201 + Paclitaxel for ovarian cancer?
Paclitaxel, a component of the treatment, has been shown to be effective in treating ovarian cancer, especially when combined with other drugs like cisplatin. It is part of the standard chemotherapy regimen for newly diagnosed ovarian cancer patients.
12345What safety data exists for ONC201 and Paclitaxel in humans?
Paclitaxel, used in treating ovarian cancer, can cause side effects like hypersensitivity (allergic reactions), low white blood cell count, nerve damage, hair loss, and muscle or joint pain. Premedication can reduce severe allergic reactions to less than 3%. The safety of ONC201 in humans is not detailed in the provided research.
678910What makes the drug ONC201 + Paclitaxel unique for ovarian cancer?
The combination of ONC201 and Paclitaxel is unique because it explores a novel approach by combining a new agent, ONC201, with Paclitaxel, which is already a standard treatment for ovarian cancer. This combination aims to enhance the effectiveness of Paclitaxel, especially in cases where the cancer is resistant to platinum-based treatments.
25111213Eligibility Criteria
This trial is for women with certain types of ovarian, fallopian tube, or primary peritoneal cancer that's resistant to platinum-based chemotherapy. Participants should have at least one measurable lesion and be in good physical condition (ECOG score 0-1). They must not be pregnant or breastfeeding, agree to use contraception, and have adequate organ function. Those with more than four prior treatments in the resistant setting or a total of seven overall are excluded.Inclusion Criteria
I am not pregnant, not breastfeeding, and if able to bear children, I agree to use contraception during the study.
You have at least one specific spot that can be measured according to a certain set of rules.
My cancer got worse within 6 months after finishing a platinum-based treatment.
+6 more
Exclusion Criteria
I haven't had major surgery in the last 3 weeks or minor surgery in the last week.
Pregnant or lactating
I have ovarian cancer and no other active cancers requiring treatment.
+9 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive ONC201 orally on days 1, 8, and 15, and paclitaxel intravenously over 1 hour on days 2, 9, and 16. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
28 days per cycle
3 visits per cycle (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment completion
1 year
Participant Groups
The trial is testing ONC201 combined with weekly paclitaxel against these cancers. ONC201 targets specific receptors on cancer cells while paclitaxel stops their growth by various means. The study aims to see if this combination works better than paclitaxel alone for patients who haven't responded well to previous platinum-based therapies.
1Treatment groups
Experimental Treatment
Group I: Treatment - ONC201 & PaclitaxelExperimental Treatment3 Interventions
Patients receive ONC201 PO on days 1, 8, 15, and 22 and paclitaxel IV over 1 hour on days 2, 9, and 16. Cycles repeat every 28 days in the absence disease progression or unacceptable toxicity. If paclitaxel must be stopped for any reason, patients may continue on ONC201 alone.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Karmanos Cancer Institute at McLaren FlintFlint, MI
Barbara Ann Karmanos Cancer InstituteDetroit, MI
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Who Is Running the Clinical Trial?
Ira WinerLead Sponsor
References
Apatinib plus paclitaxel versus paclitaxel monotherapy for platinum-resistant recurrent ovarian cancer treatment: A retrospective cohort study. [2022]Apatinib, an oral antiangiogenic drug, exerts potential anti-tumour effects on platinum-resistant recurrent ovarian cancer (PROC). This study intended to evaluate the efficacy and safety of apatinib plus paclitaxel compared to paclitaxel monotherapy in PROC patients.
Chemotherapy of advanced ovarian cancer: current status and future directions. [2015]The identification of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) activity in previously treated patients with ovarian cancer has led to its incorporation into primary chemotherapy regimens for newly diagnosed patients. Based on prospective trials by the Gynecologic Oncology Group, paclitaxel/cisplatin has become the new standard regimen in the United States. A confirmatory trial has been performed by Canadian-European investigators. Clinical trials are in progress evaluating strategies to optimize paclitaxel-based chemotherapy. Randomized trials also are in progress, both in the United States and in Europe, comparing cisplatin/paclitaxel versus carboplatin/paclitaxel. Other trials are evaluating the role of paclitaxel dose intensity, the schedule of infusion, and the role of interval debulking surgery. In addition, pilot studies are under way to evaluate high-dose therapy together with peripheral blood stem cell support. Intraperitoneal cisplatin has been shown to be superior to intravenous cisplatin when administered together with intravenous cyclophosphamide. A combination of intravenous paclitaxel and intraperitoneal cisplatin has been compared with intravenous cisplatin and paclitaxel.
Chemotherapy vs tamoxifen in platinum-resistant ovarian cancer: a phase III, randomised, multicentre trial (Ovaresist). [2018]Chemotherapy in platinum-resistant ovarian cancer (PROC) aims for palliation and prolonging of progression-free survival (PFS). This study compares Health-related Quality of Life (HRQoL) and efficacy between single-agent chemotherapy and tamoxifen in PROC.
The Gynecologic Oncology Group experience in ovarian cancer. [2022]Trials performed in the past 15 years by the Gynecologic Oncology Group identified as optimal a platinum/taxane combination as the backbone to treat chemonaive ovarian cancer. Comparison to a triplet adding a third drug to the backbone is least likely to significantly improve outcome, however, of the drugs currently available for addition; doxil, etoposide, gemcitabine, and topotecan; none appears to be any better or worse than was paclitaxel a decade ago. An approach more likely to improve outcome would be to incorporate as many of these "new" drugs as possible using sequential doublets. Some doublets have a better biochemical rationale such as cisplatin and gemcitabine (inhibition of DNA repair) or topotecan and either doxil or etoposide (upregulation of topoisomerase II levels by topotecan followed by a topoisomerase II inhibitor.
Bringing new medicines to women with epithelial ovarian cancer: what is the unmet medical need? [2022]Therapy for advanced epithelial ovarian cancer (OC) includes first line platinum/taxane-containing chemotherapy and re-treatment with platinum-containing regimens for disease recurrence in patients likely to respond again. Single-agent, non-platinum, cytotoxic agents are commonly used to treat patients resistant to platinum retreatment, but these agents are associated with dose-limiting toxicities and response rates below 20%.
[Neoadjuvant chemotherapy with intraperitoneal paclitaxel for advanced gynecologic cancer]. [2015]We evaluated safety and activity of intraperitoneal paclitaxel [=PTX (ip)] for neoadjuvant chemotherapy (NAC) of patients with advanced gynecologic cancer.
Options for primary chemotherapy of epithelial ovarian cancer: taxanes. [2018]The taxanes, a new class of anticancer agents, act by promoting the assembly of microtubules and stabilizing formed tubules. Two taxanes, paclitaxel and docetaxel, have clinical activity in epithelial ovarian carcinomas, including tumors with platinum resistance. Toxicities associated with the taxanes include hypersensitivity, leukopenia, neurotoxicity, and alopecia. Premedication with dexamethasone, diphenhydramine, and cimetidine decreases the incidence of severe anaphylactic reactions to less than 3%. In Phase II studies, response rates to paclitaxel in patients with previously treated ovarian cancer ranged from 20 to 48%. To date, only two Phase III study using paclitaxel in the treatment of ovarian cancer have mature data. In one trial in patients with suboptimally debulked stage III and IV ovarian cancer, conducted by the Gynecologic Oncology Group, patients receiving paclitaxel/cisplatin had a significantly greater clinical response rate and surgical response rate and a significantly smaller risk of progression than those of patients receiving cisplatin/cyclophosphamide. In a Phase III study of paclitaxel in previously treated patients at two different schedules (3- and 24-hr infusions), conducted by the Canadian-European Taxol Cooperative Group, patients on the 24-hr infusion experienced significantly more grade 4 neutropenia than those receiving the 3-hr infusion. The optimal dose, schedule, and combination for paclitaxel in the treatment of patients with ovarian cancer have not yet been defined. In Phase II studies of docetaxel in patients with previously treated ovarian cancer, response rates of 33-35% were noted. Peripheral edema was noted to be a clinically significant toxicity.
Phase I study of carboplatin, doxorubicin and weekly paclitaxel in patients with advanced ovarian carcinoma. [2020]Doxorubicin is an active compound in epithelial ovarian cancer (EOC), but adding it to carboplatin-paclitaxel causes toxicity. Toxicity can be reduced by weekly administration. We examined the tolerability of weekly paclitaxel in combination with carboplatin and doxorubicin.
Paclitaxel (Taxol)--a guide to administration. [2019]The introduction of a new chemotherapeutic agent has implications for nursing care. Paclitaxel (Taxol) chemotherapy is now being used throughout Europe for treatment of patients with ovarian cancer who have previously failed a platinum-containing chemotherapy regimen, and in many countries to treat metastatic breast cancer. Nurses need to be equipped to care for these patients receiving Paclitaxel. This paper introduces nurses to Paclitaxel, the history of its development, its mechanism of action, potential side-effects and administration. Paclitaxel's side-effects include hypersensitivity reactions, neutropaenia, peripheral neuropathy, asymptomatic bradycardia, alopecia, malaise, myalgias and arthralgias. Administration guidelines will be discussed because Paclitaxel leaches plasticizer from polyvinyl chloride (PVC) intravenous-giving sets normally used to administer chemotherapy, hence an alternative delivery system is required.
Phase I feasibility study of intraperitoneal cisplatin and intravenous paclitaxel followed by intraperitoneal paclitaxel in untreated ovarian, fallopian tube, and primary peritoneal carcinoma: a gynecologic oncology group study. [2021]Intraperitoneal chemotherapy has shown a survival advantage over intravenous chemotherapy for women with newly diagnosed optimally debulked epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. However, significant toxicity has limited its acceptance. In an effort to reduce toxicity, the Gynecologic Oncology Group conducted a Phase I study to evaluate the feasibility of day 1 intravenous (IV) paclitaxel and intraperitoneal (IP) cisplatin followed by day 8 IP paclitaxel on an every 21-day cycle.
The role of p27(Kip1) in dasatinib-enhanced paclitaxel cytotoxicity in human ovarian cancer cells. [2021]Less than 50% of ovarian cancers respond to paclitaxel. Effective strategies are needed to enhance paclitaxel sensitivity.
Paclitaxel (Taxol) therapy in ovarian carcinoma. [2015]Ovarian carcinoma is the most common cause of death among the gynecologic malignancies. Primary therapy in advanced disease involves debulking surgery followed by platinum-containing chemotherapy. Despite such treatment, most patients die of residual or recurrent disease. Paclitaxel (TAXOL), a new antineoplastic agent, has response rates of 20% to 35% in phase II studies in patients with refractory ovarian cancer. Most women treated in these studies had platinum-resistant disease. Toxicity was primarily hematologic and neurologic. The findings from a large European-Canadian study suggest that hematologic toxicity is schedule dependent whereas neurologic toxicity is dose dependent. Dose escalation of paclitaxel with granulocyte colony-stimulating factor support and combinations of paclitaxel with cisplatin have been tested and shown to be feasible. Intraperitoneal administration of paclitaxel also is possible and advantageous from a pharmacokinetic perspective. In a multi-institutional randomized trial, primary treatment of patients with suboptimal disease with the combination of paclitaxel and cisplatin was compared with cyclophosphamide and cisplatin. Toxicity data from this completed trial show paclitaxel to be safe in this setting. Efficacy awaits maturity of survival data. Future clinical development of paclitaxel will include its use in less bulky disease and further evaluation of its dose escalation in advanced platinum-resistant disease. Paclitaxel currently is considered first-line treatment for platinum-resistant ovarian carcinoma. Further clinical investigation will determine its role in the primary management of ovarian cancer.
Treatment of ovarian cancer: current status. [2015]Cytoreductive surgery followed by platinum-based combination chemotherapy has been standard therapy for patients with advanced epithelial ovarian cancer. Despite advances in surgery and in the development of a less toxic platinum compound (carboplatin), most patients with advanced ovarian cancer are not cured. Current clinical trials focus on dose-intense chemotherapy, routes and schedules of administration, and the role of paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ). This novel agent has been shown to be highly active in patients with platinum-resistant ovarian cancer. Paclitaxel together with platinum (ie, cisplatin or carboplatin) combinations are now being tested in prospective randomized trials and in pilot studies in previously untreated patients with advanced disease.